Muscle metabolism during exercise in young

and older untrained and endurance-trained men
ANDREW
R. COGGAN,
AMIR M. ABDULJALIL,
SCOTT C. SWANSON,
MARGARET
S. EARLE,
JAMES W. FARRIS,
LISA A. MENDENHALL,
AND PIERRE-MARIE
ROBITAILLE
Exercise Physiology Laboratory, School of Health, Physical Education, and Recreation, and Departments
Radiology and Medical Biochemistry, The Ohio State University, Columbus, Ohio 43210
COGGAN,ANDREW R., AMIR M. ABDULJALIL, SCOTT C.
SWANSON,MARGARETS.EARLE,JAMES W. FARRIS,LISA A.
MENDENHALL,AND~IERRE-MARIEROBITAILLE.MUX~~
metabolism during exercise in young and older untrained and endurance-trained men. J. Appl. Physiol. 75(5): 2125-2133, 1993.To examine effects of aging and endurance training on human
muscle metabolism
during exercise, ‘lP magnetic resonance
spectroscopy was used to study the metabolic response to exercise in young (21-33 yr) and older (58-68 yr) untrained
and
endurance-trained
men (n = 6/group).
Subjects performed
graded plantar flexion exercise with the right leg, with metabolic responses measured using a ‘lP surface coil placed over
the lateral head of the gastrocnemius
muscle. Muscle biopsy
samples were also obtained for determination
of citrate synthase activity. Rate of increase in Pi-to-phosphocreatine
ratio
with increasing power output was greater (P < 0.01) in older
untrained
[0.058 k 0.022 (SD) W-l] and trained men (0.042 t
0.010 W-‘) than in young untrained
(0.038 t 0.017 W-l) and
trained men (0.024 k 0.010 W-l). Plantar flexor muscle crosssectional area and volume (determined using ‘H magnetic resonance imaging) were ll-12%
(P < 0.05) and 16-18% (P < 0.01)
smaller, respectively, in older men. When corrected for this
difference in muscle mass, age-related differences in metabolic
response to exercise were reduced by -50% but remained significant (P < 0.05). Citrate synthase activity was -20% lower
(P < 0.001) in older untrained
and trained men than in corresponding young groups and was inversely related to Pi-phosphocreatine
slope (r = -0.63, P < 0.001). Age-related
reductions in exercise capacity were associated with an altered muscle metabolic response to exercise, which appeared to be due to
smaller muscle mass and lower muscle respiratory capacity of
older subjects. Endurance
training
was associated with 60100% higher muscle citrate synthase activity and improved metabolic responses in young and older men but apparently could
not prevent an age-related decrement in these variables or an
age-related decrease in muscle mass.
aging; master athletes; muscle atrophy;
netic resonance spectroscopy; magnetic

citrate synthase; magresonance imaging

MUSCULARENDURANCE
in rats( 11,15)
and humans (10). In rats, this increase in muscle fatigability with age appears to be due, at least in part, to an
altered metabolic response to exercise (2, 11, 13, 15, 25).
Thus the muscles of older rats undergo greater depletion
of ATP, phosphocreatine (PCr), and glycogen and accumulate more lactate during electrical stimulation of the
motor nerve than the muscles of young rats (11,15). SimiAGINGREDUCES

0161-7567/93

$2.00

of

larly, the rate of muscle glycogen utilization during
treadmill running is greater in older rats than in young
rats (2). These differences between young and older rats
in the metabolic response to exercise appear to be largely
the result of an age-related decrease in skeletal muscle
mitochondrial respiratory capacity (1, 2).
Little is known about the effects of aging in humans on
the metabolic response of skeletal muscle to exercise. We
have found, however, that mitochondrial marker enzyme
activities are 15-30s lower in the muscles of healthy but
sedentary older (60-70 yr) subjects than in those of
young (20-30 yr) subjects (9). Similarly, others have reported that the capacity of human muscle to utilize O,,
measured in vitro using either whole muscle homogenates (26, 34) or isolated mitochondria (34), is 25-50%
lower in older subjects. It therefore seemspossible that,
as in rats, an age-related reduction in human muscle respiratory capacity could alter the metabolic response to
exercise and thus contribute to the reduction in muscular
endurance observed in older subjects (10). In keeping
with this hypothesis, McCully et al. (24) reported that
the rate of muscle PCr resynthesis after exercise is significantly reduced in older subjects. Others, however, found
no effect of aging on human muscle metabolism during or
after exercise (33). Thus, whether aging alters muscle
metabolic responses during exercise in humans remains
uncertain.
Reduced skeletal muscle respiratory capacity and altered metabolic responses during exercise in older rats or
humans may be due to a decrease in habitual physical
activity rather than the aging process per se. In support
of this hypothesis, young and older rats that have been
trained using an identical exercise program have similar
muscle mitochondrial respiratory capacities and use similar amounts of muscle glycogen during exercise (1,2). In
older men and women, we found that endurance exercise
training increases muscle mitochondrial marker enzyme
activities by ~50% (8), and Meredith et al. (26) demonstrated an even larger training-induced increase in in vitro muscle respiratory capacity. It is not known, however, whether endurance training of older humans can
prevent or ameliorate possible age-related alterations in
muscle metabolism during exercise.
The purpose of the present study, therefore, was to
determine the effects of aging and endurance training on

Copyright 0 1993 the American Physiological Society

2125

Whereas these men were competitive in local and correct for the possible effects of age-related muscle atroregional endurance competitions. 128 X 256 matrix.ducted 26 h after the subjects’ last meal and.
Running
distance. The
Values are means -t SD.meter (Rayfield RAM-9200).Magnetic Resonance Facility.
walking short distances).
sports such as distance running or cycling. These latter measurements could not be performed in conjunction with the subsequent 31P-MRS exever.5-T instruswimming. To
cyclist. six young (27 t 4 yr) trained men.col
.8 X lo-mm
180 km cycling. Total
resolution. most had not achieved phy on the metabolic response to exercise.. Muscle biopsy sam.
h/wk
6
7+2
B&4
tions. Running and/or
tween the femoral epicondyles and the calcaneus was
cycling pace. 0.. and some participated in recre. 42 km running) after this study.2126
AGING
AND
HUMAN
MUSCLE
1.6 X 0. was used to determine maximal 0. for the
ing of two runners. km/wk
4
137+77
190+114
Cycling pace. the cross-secsuccesson a national level and would not be considered tional area and total volume of the plantar flexors were
first determined using ‘H magnetic resonance imaging. was greater in the young athletes first determined by acquiring several sagittal images. None. subjects were studied at the
hand.ercise. TR (repetition
third in the Hawaii Ironman Triathlon (4 km swimming. driving.
to be elite athletes. max. and six fold measurements (19). To ensure that 7j02max
had &indeed been
Subjects and preliminary testing. 224 h after their last training session. On the other
Approximately 1 wk later. despite an increase in treadmill
community publications and media. Preliminary testing included a medical history. m8x.g.
tronic 0. All untrained subjects tial study served to minimize possible learning effects
and also enabled quantification of the subjects’ heart
performed normal daily activies (e.001) different
from
first test. at least two of the following criteria had to be
cruited through advertisements placed with campus and
met: a plateau in VO. we used 31Pmagnetic resonance spectroscopy (31P. km/wk
5
55+19
56+24
physical examination.
cardiovascular abnormalities. After premaximal heart rate. km/h
4
33s
29+2*
treadmill tests to volitional fatigue while blood pressure
and a 1%lead electrocardiogram were monitored.
human skeletal muscle metabolism during exercise. time) = 600 ms. how. uptake
MRS) to examine the metabolic response of the plantar
(VO 2.ally adjusted running test to fatigue to determine VO.In the young and older subjects. shopping. The young subjects performed only an individuflexor muscles during exercise in young and older un.). Subjects were rereached. whereas the second test. of excitations). however. Subjects first perolder (62 t 2 yr) trained men were enrolled in the study.
liminary screening of health status (seebelow). was used to screen for
young trained
men.. or musculoDuration
of training. The older subjects also underwent two graded
Cycling distance. a respiratory exchange ratio >l. metabolic. None was taking prescription medicaTotal training
volume. and CO.g. Training duration. however. and pace in young
and older trained men
METABOLISM
DURING
EXERCISE
was approved by The Ohio State University Human Subjects Review Committee.5 km Imaging was performed with a GE Signa 1. and VO. six older (63 t 3 yr)
untrained men.
Young
Older
All subjects were normotensive nonsmokers who were
n
Trained
Trained
free of detectable cardiovascular. six young
Body fat and fat-free mass were estimated from skin[25 t 2 (SD) yr] untrained men. using a Bruce protocol. whereas another older standard multislice multiecho sequence. km/h
5
1421
12+1*
test. was defined
METHODS
as V0.
than in the older athletes (Table 1). The mean of the
two highest consecutive 30-s values for VO. mixing chamber.
yr
6
12+6
12+5
skeletal disease. To using an individually adjusted walking or running protodo so. held a job requiring strenuous physical labor or properiment. Experiments were conmost continuously for Z-20 yr. both the young and older trained men had been
training for and/or competing in endurance sports al.
trained and endurance-trained men. This iniwhereas most of the older men were employed in or retired from professional careers. tennis). 40 km cycling. The distance beand the older trained men (Table 1). respectively).
below)
at
the Exercise Physiology Laboratory. * Significantly
(P < 0.
had won the World Triathlon Championship (1. The study protocol
Without moving the subject. 1. blood pressure. 10 km running) in his age ment and a quadrature detection body coil with use of a
group -1 yr before being studied. and none participated in endurance
the use of ferrous metal equipment. Endurance-trained
speed and/or grade.. and elecity and metabolic responses during exercise.
subjects were also recruited using the published results of
or a heart rate within 10 beats/min of age-predicted
local running and/or triathlon competitions. One of the older athletes. during plantar flexion exational sports or games (e.lO.
Magnetic resonance experiments. Parameters
athlete had finished fourth in the same event and placed were as follows: TE (echo time) = 20 ms. The subject was
years of training and average weekly training volume did placed in the magnet in the supine posture with the right
not differ significantly between the young trained men leg positioned in the center of the coil.
and one trained men. 35-40 sequential transaxial
TABLE
. with both groups consist.
formed
the entire plantar flexion exercise protocol (see
Most of the young men were university students. three duathletes/triathletes. and all subjects provided informed written consent. (ZO). uptake (vo2)
was
ples were also obtained from the lateral gastrocnemius measured every 30 s during exercise by use of an automuscle to examine the possible relationship between mated open-circuit system that incorporated a dry gas
age-related changes in mitochondrial respiratory capac. squash. 2 NEX (no. analyzers (Applied Electrochemistry
S3-A and Beckman LB-Z.rate. and a 75-g oral glucose tolerance
Running
pace. because the powerful magnetic field precluded
longed walking. volume.

The. despite strong verbal encouragement.. This device consisted of a wooden foot pedal and
a cable-and-pulley
system arranged so that plantar flexion from 0’ (vertical) to 24” raised a weight 10 cm. 5
mM . carefully excluding all visible noncontractile tissue
(i.AGING
AND
HUMAN
MUSCLE
METABOLISM
images (10 mm thick. flexor digitorum long-us. Briefly.02% citrate-free
bovine serum
albumin (BSA). The three areas quantified were I) the lateral gastrocnemius.
resonance
spectra acquired
of’ a young endurance-trained
flexion exercise (3-27 min). The citrate formed was then measured fluorometri-
DURING
2127
EXERCISE
ATP
CP
0 min
__h__ihc?s*_ij_l
9 min
12 min
@--++fi
-A-
15 min
27 min
10
2
-6
-14
-22
-30
PPm
FIG. and a wide strap was placed
tightly over the waist and upper thighs to minimize horizontal or vertical movement. diet and exercise
controls were again imposed as described above. 0. 1. Partially saturated 31P spectra
were acquired during the last -60 s of each exercise
stage with use of a 2-s TR.
0.5 mM EDTA.
Data analyses.1. 1. Thereafter. The latter area included the soleus. ‘lP magnetic
gastrocnemius
muscle
min) and during plantar
phate. and the coil was tuned to 31P.4) containing 0. the power output was increased by
0. and
(where present) plantaris but excluded the popliteus and
peroneus longus and brevis.
This second strap also
served to keep the knee fully extended. as previously described (5-9).
from right1 lateral
man at rest (0
CP. blood vessels. 20 averages/
spectrum.
NY). thereby maximizing involvement
of the gastrocnemius
muscle (31). Citrate
synthase activity was measured by adding 2 ~1 of the
diluted homogenate to 50 ~1 of assay reagent [50 mM
tris(hydroxymethyl)aminomethane
buffer. 5). and excess oxaloacetate was destroyed by adding 5 ~1 of 0. Once the magnetic field had been shimmed. tendons.
500 PM oxaloacetate. which was maintained
for 3 min. a 2-kHz sweep width. and then
stored at -8OOC until subsequently
analyzed for citrate
synthase activity (4) and protein content (2l).25% BSA] and
incubating at room temperature
(24 t O. ‘H magnetic resonance imaging scans
were printed on film and digitized using a video analysis
system. flexor hallucis longus. A 4cm-diam
31P-tuned surface coil was
positioned directly under the lateral head of the subject’s
right gastrocnemius
muscle and secured to the leg with
adhesive tape. For each image. 31P spectra were acquired
at 25. CA). and a l-kilobyte
block
size. and a
muscle biopsy sample was obtained from the lateral head
of the right gastrocnemius
muscle by use of a 5mm
Bergstrom
needle (Stille-Werner.75 W every 3 min until. The subject then began
performing repeated plantar flexions at a rate of 3O/min
(paced by a metronome)
using a custom-built
exercise
device.
fat). 400
PM acetyl-CoA. The
initial power output was 0. creatine phos-
tally using citrate lyase and malate dehydrogenase. thereby minimizing movement of the leg within the magnet.02% BSA. 1 mm interspacing)
were then obtained covering this linear distance (total scan time -10 min). The subject was then repositioned within
the magnet.
The metabolic response to exercise was then studied
using 31P-MRS. as
previously described in detail (4. tibialis posterior. 2) the medial gastrocnemius. both fully relaxed
(10-s TR) and partially saturated (2-s TR) 31P spectra
were acquired before exercise. Jandel Scientific.
Muscle biopsy.0) containing 0. The axis of rotation of the foot pedal was
positioned at the ankle joint. Each cross-sectional area
. nerves. Total exercise duration ranged from 12
to 30 min (4-10 stages). Corta
Madera.
Protein concentration of the homogenate was measured calorimetrically
(21) using BSA as the protein
standard. a 5.to lo-mg portion of
each sample was homogenized in 50 vol of 20 mM sodium
phosphate buffer (pH 7.86 MHz by use of a l-pulse sequence. pH 8. To correct for saturation
effects. On a subsequent day.5 N NaOH and boiling for 5
min. This
weight also served to return the pedal to O” after each
movement. and 3) the remaining plantar flexor muscles of the posterior compartment. This system consisted of a light box and a video
camera interfaced with a laboratory computer operating
commercial software (JAVA. Representative
spectra acquired from a young trained subject at rest and during
exercise are shown in Fig.75 W.
Ronkonkoma. An aliquot of this homogenate was then diluted further (20-fold) with 20 mM
imidazole buffer (pH 7.muscle specimen was frozen in liquid N.8-mercaptoethanol. and 50% glycerol.e. connective tissue. The foot was secured
to the pedal with a strap. the cross-sectional areas
of three separate regions were determined by manually
tracing the desired muscle area with a mouse-driven cursor. the subject was I) unable to maintain the cadence
or 2) unable to move the foot pedal over the required
range of motion. The
reaction was stopped.I”C) for 1 h.

consequently. data for the
young and older untrained and trained men are presented separately as means t SD. however. cm2/W. Percent body
fat.001.the effect of training were statistically significant (P <
vided that ATP and H+ are constant (3). 2). was significantly higher
metabolic stress (3.. Despite a similar age differential. The volume of each imaged subjects. regardless of training status.50 t 0.
the calcaneus and especially the popliteal space. muscle volume
(W/l). PCr.89 t 0. Total plantar flexor
trained men were somewhat smaller (32 and 22% for l/
muscle volume (in liters) was calculated by summation of min and ml min-’ kg-‘. l/W.001) in the older untrained men than in the young unware (GE) to give relative concentrations of ATP (cu. the trained
was measured three to eight times. These analyses were performed
with power output expressed
in
absolute
terms (W) and relative
to muscle cross-sectional
area (W/
cm2).68 t
measure because both the numerator and denominator
0. This is most likely
training may slow the fall in maximal heart rate with
due to an inadequate signal-to-noise ratio in the 31P age (28). 3. consistent with their roughly four-decade
and y peaks).2128
AGING
HUMAN
MUSCLE
m
0. no significant interaction effects were observed. howlated by measuring the PCr-P. 1.recent longitudinal data. regardless of age.e.interaction between the effects of aging and the effects of
ments.5 t 8.& trained men.62 in the older
of this ratio reflect changes in bioenergetic status.
signal before Fourier transformation.3 t 6. Intracellular pH was calcu. this ratio remains an accurate gross measure of young trained men (54.only 20 beats/min less (P < 0. Significance was untrained men (0.
Because P. Peak areas were
Maximal heart rate was ~40 beats/min lower (P <
integrated by a blinded technician using commercial soft0.
and peak plantar
flexor
power (%peak
power). and as such we have used this ratio
ences in muscle cross-sectional area were greater near
while recognizing its shortcomings.liters per minute or in milliliters per minute per kiloculated assuming that each such nonimaged segment had gram.05) than
terpreted in terms of thermodynamically significant reac. and
Changes in Pi/PCr under equilibrium conditions have 5.20
training were obtained for a number of variables. 22) (Fig.(48.
indicating that the effects of aging were generally similar
in the untrained and the trained men.25
-
m
I
n
I
R
0. we chose it as a more sensitive ity (in mol h-l kg muscle protein-‘) averaged 3./PCr
with
increasing
power output
(i. Physical characteristics of the
subjects are shown in Table 2.
As a result of this lower body fat content. Although Pi/ATP and (P < 0. Howliters).
0.99 in the young trained men.e. being higher in the older than in the young men
but lower in the trained than in the untrained subjects. AlPCr/ATP are more directly relevant from a thermodythough based on a relatively small number of subjects.those in the young untrained men (56. furthermore. pH decreased during
Maximal plantar flexor cross-sectional areas in the older
exercise../PCr is unitless.
endurance training on VO 2maxwas not statistically signifiA ~-HZ line broadening was applied to the “lP-MRS
cant (P = 0. although changes in Pi/PCr cannot be easily in.5
’
. whereas P.00
’
0.5 cm2). untrained men.
however.05. respectively). The than in the young untrained men. and Pi.9 cm2) were ll-12%
smaller (P < 0.
3.75
-
1 0.5 t 4. The rate of increase in the Pi/PCr ratio with in. The P values reported here therefore refer to these significant main effects./PCr may be less thermodyMuscle citrate synthase activity. whether expressed in
volume of muscle between the imaged segments was cal.01) than that of the young
creasing power output was used as an indicator of muscle trained men and. respectively). Neveruntrained men (49.0
Power
’
4. The effect of age and
been theoretically linked to changes in free ADP. 10 mm). with an average coeffisubjects weighed significantly less than the untrained
cient of variation of ~2%. but this apparent
the volume of the imaged and nonimaged muscle seg.
respectively.09 t 0.01) than that in the young untrained men (1.
Physical characteristics.44 in the older trained men.0 cm2) and older trained men
theless. chemical shift difference
ever.62 t 0. It is uncertain.
namic perspective.05 and P < 0. Pi/PCr
slope) was calculated
by regression analysis (solid line) and was used as an index of muscle metabolic
stress.5 t 6.52 in the young untrained men.
1.5
. Data were analyzed using two-way
quently.5 cm2) and
tions. maximal heart rate of the older trained men was
(30). Relationship
of Pi/PCr
to power output
for subject whose
data are shown in Fig. on the other hand.021
n
:
R=0.50
0
-. Thus. Initial
linear rate of increase in P. Citrate synthase activnamically appropriate. ConseStatistical analyses. albeit only near fatigue (see RESULTS).099+0.0
(W)
RESULTS
2. and %peak power-‘.05) than that in the older untrained men.14). pro.
muscle segment was calculated by multiplying the crossvo 2max was -45% lower in the older untrained men
sectional area by the image thickness (i. 7.
FIG.96
2
AND
*x
n
n
0.0
’
’
.difference in age. total plantar flexor muscle volume in the older
(age X training) analyses of variance. differed with age and with training
status. Significant main effects for age and 0. These values are almost identical to those obever..20 t 0.
Y=0.
corresponding
slopes have units of
W-l.
6.13 liter) was 18% lower (P <
defined as P 5 0.
in the present studies. For comparison purposes.
’
METABOLISM
DURING
EXERCISE
SULTS). Differences in VO 2maxbetween the young and older
the shape of a truncated cone (27). (27) using computed tol
l
l
l
. with the exception of maximal heart rate (see RE. Age-related differbioenergetic status. differences between groups in these these cross-sectional observations are consistent with
ratios did not achieve statistical significance when ana. whether equilibrium conditions were achieved
Plantar flexor muscle cross-sectional area and volume.
spectra.tained previously by Rice et al. suggesting that endurance
lyzed as a function of power ouput. The older men were significantly shorter and had a lower fat-free mass than the
younger men.

6620. was measured at rest and during plantar flexion exercise during
the initial experiment performed at the Exercise Physiology Laboratory.33
52. averaging 7.1
22.001
P < 0. Fig. The Pi/PCr slope (in W-‘) was inversely related to muscle cross-sectional area (r = -0. 7.
P < 0. Resting VO.
kg
Body fat.
2-way (age X training)
analysis of variance. Subject characteristics
Untrained
Trained
Young
Height.5-tl.03 in the older trained men. kg
VO
DURING
Age
Effect
Older
Young
Older
177-t9
77.4k9. was -20% lower (P <
0.ut during
exercise. %
Fat-free
mass.001) in older
untrained
and trained
men than in young untrained
and trained
men. B and
C).
Responsesduringplantar flexion exercise.) are presented
for the first 4 exercise stages.2k5. 4). 5. 50). (AVO. Fig. with plantar
flexor volume averaging 0.6 t 1. although Pi/PCr increased
more slowly in athletes than in nonathletes regardless of
age.0
57.6k5.13 liter in the older
trained men compared with 1.SD for 6 subjs/group
in ml/min.63 (P < 0. During exercise. cm
Weight.12 t 0. A similar difference existed between the
young and older trained men.0
P < 0. 0.001
P < 0.1t6. Similar results were obtained when power output was expressed relative to peak plantar flexor power (Fig. especially in the
trained men.9
64.15 t 0.01) than in older untrained
mography. and 7.0
15. Thus the mean Pi/PCr slope during exercise differed
significantly with age (P < 0.9
7.06.5-tl.
5A). When power output was expressed
relative to muscle cross-sectional area or muscle volume
to correct for the reduced muscle mass of the older men. maximal
0.0* 14.001) to the Pi/PCr slope (expressed in
W-l). the latter correlation
coefficient increased to r = -0.
ii0 2 max. the
P..62kO. P < 0.
respectively. At rest. When power output was expressed relative to muscle cross-sectional area or volume.8
199+9
2.05 t
0. indicating that the reduced muscle volume of the
older men was not simply due to their smaller stature. P < 0. P < 0. these differences were not statistically significant because of large intersubject variability and/or
the small number of subjects in each group.9 at fatigue (Fig.001) in the older untrained and older trained men than
in the corresponding young groups (Table 3).1 t 0. 3.001
P values
refer
to significant
main effects
bY
men.4
54. beatslmin
l
l
Val ues are means -t SD for 6 subjs/group.4k9.03. Fig.
Peak plantar flexor power averaged 4.. This difference is probably partially due to the lower fat-free mass
of the older subjects.7
11.001
P < 0.8 W in the young trained men.4k5.
DISCUSSION
Numerous studies have demonstrated that the reduction in exercise capacity that accompanies aging is asso-
.
Resting muscle pH did not differ with age or with
training status..3
170s
74.7 W in the older untrained
men. 3A).5
179k5
70. * Significantly
lower (P < 0.064).05). Although muscle
pH tended to decrease earlier but to a lesser extent in the
older subjects. P < 0. similar results were obtained when power output was expressed relative to peak plantar flexor power
(Fig.001. as assessedusing 31P-MRS (22).
differences between the young and older subjects in the
metabolic response to exercise were reduced by -50%
but remained significant (P < 0.6k4. At any given power outp.Ok2.02 t 0. and
0. 0.19kO. uptake. VO. 6.6 t 0.05).
m aximal heart rate.9
W in the older trained men and was inversely correlated
(r = -0.2k4.86 t 0.14-t0.02 in the older
untrained men.04 in the young trained men.2k4.
Data for increase in VO. Muscle pH did
not change during the initial stages of exercise but then
decreased to -6. the increase in whole body VO.7
169&6*
P < 0.26
29.001
I’ < 0. however.0 W in the
young untrained men. 3.10 t
0.
P < 0. and 4.05.51. however.AGING
TABLE
AND
HUMAN
MUSCLE
METABOLISM
2129
EXERCISE
2.02 in the young untrained men.07 t 0.001
P < 0. Resting %2 and increase in L%I~above resting
during one-leggedplantar flexion exercise
TABLE
Ai’02
Stage 1
Stage
2701~25
205+21*
44+15
30+18
79+17
63+24
113221
96+35
147+27
128k46
277219
223+20*
34+20
34+18
75222
71+22
115k25
108k30
176~~51
143+37
Resting
Untrained
Young
Older
Trained
Young
Older
VO.01. B and C).
2
Stage
3
Stage
4
Values-are
m$ans -t.001
2 max
l/min
ml min-’
kg-’
HR max. These results are in keeping with prior observations indicating that maximal exercise capacity is inversely related to muscle metabolic stress during submaximal exercise.
Training
Effect. above
resting was not significantly different among the four
groups (Table 3).01) and with training status
(P < 0.10 t 0.03 t 0.05
P < 0.9 t 0. 30). Fig.324.38
66.48.05
P < 0. muscle volume (r = -0.
output in the older untrained men than in the young
untrained men.
The subjects were subsequently studied at the Magnetic Resonance Facility. Again.1k5. Pi/PCr averaged 0.4
189&6
3. Although Pi/PCr
tended to be higher in the older subjects.10 liters in the
young trained men.
Relationship between metabolic responsesand skeletal
muscle characteristics.01
3.49
47. and
muscle citrate synthase activity (r = -0.7
65. Differences in muscle volume between young and older subjects were only slightly reduced (to 12-13%.04.05) when the data were expressed relative to height or tibia1 length (data not
shown).
* Significantly
higher (P < 0.55./PCr ratio rose more rapidly with increasing power
3.
HR. A similar age-related difference in muscle volume was observed in the trained subjects. this difference did not achieve statistical
significance (P = 0.03 in the four groups. which
were completed
by all subjs.70.3k4.7
155t9
4. 7.05.06 t 0.9
16825
61.

was chosen in part because it facilitated
noninvasive assessment of muscle metabolism using 31PMRS. at any given absolute power output.11. young untrained
men. because exercise efficiency (as
indicated by the relationship
between VO.040
it
0
PcO.05
PcO. It is
unlikely that the absolute rate of ATP hydrolysis
was
higher in the older men. and power
output during plantar flexion exercise) did not differ
with age. as measured
by peak power output.13.
Consistent with previous studies of aged rats (2. Thus a greater demand for ATP per unit of
muscle tissue probably contributed
to the altered metabolic response of the older subjects during exercise. Muscle pH also tended to decrease at a lower power
output in the older subjects.13.
The
purpose of the present study was to determine whether
aging also affects muscle metabolism during exercise in
humans and. however. suggest that decreases in Vo2max and alterations in
skeletal muscle metabolism contribute to the deterioration in exercise capacity with aging (2. although this latter difference was not statistically
significant.05
0. we found that aging apparently altered the metabolic response to exercise in humans.
Changes in Pi and PCr concentrations
during exercise
reflect the balance between the rate of ATP hydrolysis
and the rate of ATP resynthesis.
a slower rate of
ATP production.
The physiological
importance
of this greater disturbance
to energetic homeostasis during exercise is demonstrated
by the significant correlation between the Pi/PCr slope and the exercise capacity of the plantar flexor muscles.060
h
raining:
PcO.20
Training:
g 0.05
PcO. Standard
deviations
(typically -0.020
CL
2
0. muscle volume
(C).25).10
pH units) have been omitted
for clarity.000
Age:
:
Q
Y
1
Power
(W)
FIG. 30). although at
rest Pi/PCr did not differ significantly
between the young
and older men.11. Martin et al.
7. older trained
men. one-legged
plantar flexion. older untrained
men.
or a combination
of these factors. Indeed. i. 4.05
PcO. Studies of rats. In
.
young trained
men.
l&25)..
Thus the altered metabolic response of the older subjects could theoretically
be
due to a faster rate of ATP utilization.15. to ascertain whether this effect could
be prevented or ameliorated by endurance exercise training.
the rate of ATP hydrolysis per gram of muscle was probably higher in the older men because of their smaller muscle mass. However. Significant
main effects
analysis of variance
regardless
of whether
power output
was expressed
cross-sectional
area (B).
ciated with a decrease in VO 2max resulting from a decline
in central cardiac function (cf. during exercise Pi/PCr increased more
rapidly with increments in power output in the older subjects.2130
AGING
AND
HUMAN
MUSCLE
METABOLISM
DURING
EXERCISE
A
Age:
0. H.05-0. The exercise model that we used. or peak power (D).
6
s 0.01
L
Young
Untrained
Old
Untrained
Young
Trained
Old
Trained
Young
Untrained
Old
Untrained
Young
Trained
Old
Trained
0.01
g 0. Intramuscular
pH during
plantar
flexion
exercise in the 4
subject groups: l .001
0
v)
Young
Untrained
Old
Untrained
Young
Trained
Old
Trained
FIG. Thus. however. 0. 0. This model was also chosen. because the
metabolic response to exercise with a small muscle mass
would be less likely to be influenced by the age-related
decline in maximal cardiac output. if so.002
Q
sw
z
6 0. X Mean
Pi/PCr
slopes during exercise.e.05
PcO.000
L--
Young
Untrained
for age and training
in absolute
terms
Old
Untrained
Young
Trained
Old
Trained
status were indicated
by
(A) or relati ve to muscle
(23) demonstrated
that maximal calf muscle blood flow is
unaffected by aging in healthy men.060
Age:
Training:
h
3
2
PcO.01
Age:
Training:
PcO.

.*
0
0. 34) [but not all (14)] prior investigations
have found that muscle respiratory capacity is reduced in
older subjects.. Peak
plantar flexor power was also higher in the young trained
men. * . and older
trained
men (0). muscle volume (C). Relationship
between
citrate
synthase
activity
of lateral
gastrocnemius muscle
and Pi/PCr
slope during
plantar
flexion
exercise
in young
untrained
men (o). . E.080
-&
A
0
0 .OOl
0.o.060
o
g 0. the latter adapation to endurance training has not
been previously demonstrated in older humans. significant differences remained between the young and older subjects. Little attention
has been directed. in addition to studying young and older sedentary individuals.
o
*. young trained
men (m).
. Although expected on the basis of studies of young individuals.000
’
-
’
2
-
4
’
*
6
’
.000
MUSCLE
METABOLISM
B
DURING
0
0
r
.98.
O. because maximal voluntary torque per unit of muscle cross-sectional area or volume did not differ with age
(12).
0.99. Factors in addition
to a reduction in contractile tissue must therefore have
contributed to the altered metabolic response and reduced exercise capacity of the older men.
*.000
0
a.*.
n n
0 * .
inasmuch as citrate synthase activity was 13 and 25%
lower in the older untrained and older trained men than
in the corresponding young groups. toward the effect of this decline in muscle mass on metabolic responses and performance during dynamic exercise requiring submaximal
force production. The
benefits of endurance training are emphasized by the fact
that.000
’
2
Citrate
-
’
.001. As expected.000
3. 26).
EXERCISE
2131
R--0. * . these correlations
were almost perfect (r = -0.001
-
R--0.
we also studied young and older men who were training
vigorously for endurance competitions. *. or
peak power (U).63
P<O. *. P < 0.P. * . 0
. in absolute terms.
4
synthase
keeping with this hypothesis. *.
muscle respiratory capacity was roughly twofold higher
and the Pi/PCr slope was substantially lower in the
young trained men than in young untrained men.
0
AND
H UMAN
-r‘
s
$
-0
g
I+-0.55
PKO. One likely factor is muscle mitochondrial respiratory capacity.000 ‘I
2
Citrate
-
’
4
synthase
-
’
6
activity
*
’
8
(mol/h/kg)
.AGING
0. *.55
P<O. P < 0.02 and r = 0. R. cf. This also appeared to be true in the present subjects. Therefore.
Alterations in muscle mass and muscle respiratory capacity (and therefore in exercise metabolism) with advancing age could be due to a reduction in habitual physical activity rather than aging per se. 2).001 and r =
0. 26. the Pi/PCr slope and peak plantar flexor power of the older trained men were similar to
. respectively) when variability was reduced by using group mean data instead of individual data in the
calculations. Muscle respiratory capacity and peak plantar
flexor power were also higher and the Pi/PCr slope was
also lower in the older trained men than in the older
untrained men. differences in the Pi/PCr
slope between the young and older subjects were significantly reduced when corrected for differences in plantar
flexor muscle cross-sectional area or volume. . This is unlikely to
have been due to a greater amount of noncontractile (i. respectively). however.
’
IO
6
a.
FIG. unpublished observations).
’
10
(mol/h/kg)
ity with aging plays a major role in the altered muscle
metabolism and impaired exercise performance of older
animals (1. An age-related reduction in muscle mass has long been recognized
as an important factor in the decrease in muscular
strength that occurs with aging (cf. older untrained
men
(0). The present results suggest. Alway and A.63. A significant
inverse
relationship
was
observed
whether
power output
was expressed
in absolute
terms (A) or relative
to muscle crosssectional
area (B).020
* .
cL 0. P < 0.001.66.ooo’l
10
-
0
0 *
*
’
4
2
0
*
’
6
*
’
8
*
’
10
h
‘L
C
-2
1
0
0.
3. This was also true in the present subjects.
g
-
V
g 0.
0
0
z
8
0
*. 16). provided that the training stimulus is adequate (8.e. .
0
0
n
n
0
I
-.002
0.
fat or connective) tissue in the muscles of the older subjects.63
P<O.Ol
o
•I
4. * 0.003
W-0.0
8
* . Indeed. . inasmuch as both the Pi/PCr slope and peak
power output were significantly correlated with muscle
citrate synthase activity (r = -0. P <
0.OOl
0
2
a
0. 0 . 5.
Coggan. 18).
8
’
3
L 1.
2
0. Studies of rats have
demonstrated that a decline in muscle respiratory capac-
’
6
activity
-
’
8
. The
mitochondrial content of muscle is an important determinant of the metabolic response to exercise (6.
-
0
*. 060
p
.01
0
0
’.
that a decrease in muscle mass with aging also plays a
very important role in the reduced exercise capacity observed under these conditions. * *
0
0 0
s
0. The higher muscle respiratory capacity
in the older trained men is consistent with prior studies
demonstrating that older subjects can adapt to endurance exercise training with an increase in muscle respiratory capacity.000
2. and
several (9. Histochemical analysis of selected biopsy samples
also revealed no differences in noncontractile tissue between the young and older men (S.
Although expressing power ouput relative to muscle
cross-sectional area or volume reduced the effect of age
on the Pi/PCr slope. Furthermore the present results suggest
that this increase in muscle respiratory capacity reduces
muscle metabolic stress during submaximal exercise.080
0
D-
z
Y
l
. though.

J. KING.
Address
for reprint
requests:
A. LOWRY. S. compared with young untrained men.
4. FARRAR. Physiol. M.
47: B71-B76. in the present study we used 31P-MRS
to study muscle metabolic responses during exercise in
young and older untrained and endurance-trained men. Mechanical
10. this appears to have been due to the fact
that plantar flexor muscle cross-sectional area and volume were 11 and 16% smaller in the older trained men
than in the young trained men.
DURING
EXERCISE
older untrained men demonstrated greater muscle metabolic stress during exercise. Physiol. S.
AND S. J.-M. E. THOMAS. The latter possibility is consistent with animal studies demonstrating that mitochondrial respiratory capacity adapts
equally in young and older muscles exposed to the same
absolute training stimulus (1). Physiol. Coggan. The
latter was true even though total duration of training and
training volume were similar in the two groups of athletes. the present
group of young trained men more closely resembles the
group of competitive young runners we studied previously who had muscle mitochondrial enzyme activities
14-23% higher than those of the older runners (7).
2. SPINA. 0..
73: 1873-1880. 0. whereas the young athletes of the present study trained and competed at higher absolute intensities than the older athletes. 45: 2915-2920.
AND J. G.. M. P. S. such that their metabolic response and exercise performance were equal to or even
slightly better than those of untrained men -40 yr
younger. Tim Kirby. 1988. HINTZ. Ageing changes in mammalian
skeletal muscle. Effects
of
detraining
on enzymes
of energy metabolism
in individual
human
muscle fibers. A. A. 0.
AND J. These findings seemingly conflict with our previous report that mitochondrial marker enzyme activities are actually higher in older athletes than in young
athletes with whom they are matched on the basis of
absolute training volume (7).
Skeletal
muscle adaptations
to endurance
training
in 60-70 year old men and women. M. 126: 107-114.
P. R.
Shriners
Burns Institute.
12.
TX 77550. In part.
properties
of young and elderly
muscle. S. 64: 259265. MCCULLY. CARTEE. R. M.. LEIGH.
11. using anthropometry. R. Metabolism
Unit. DAVIES. Physiol.
Med..
BIER.
M. Galveston. AND 0. BROWN. In this regard. A.
244 (Cell Physiol. Effect of aging and/or endurance training
on muscle strength
and volume
in men (Abstract). B. Stand. J.
1992. W.
1988. R.
D. 68: 1896-1901.
13. A.
13): C276-C287. IVY. M. Appl. the Pi/
PCr slope still differed between the young and older
trained men. KING. ALWAY. This was apparently due to
both their smaller muscle mass and their lower muscle
respiratory capacity. Metabolite
changes in aged muscle during stimulation.
264 (Endocrinol.
1986. R. P.
1983.
1984. COGGAN.
To summarize. J. HOLLOSZY. R. A. F.. M. muscle respiratory capacity.
We found that. J.
Histochemical
and enzymatic
comparison
of the gastrocnemius
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and women. E.
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AGING
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